ABSTRACT Optical imaging for small animal research is a vital imaging tool in biomedical research, and the cost, space, and time demands associated with optical imaging are less than for other imaging modalities, while the speed and relative ease of operation makes this modality very attractive for preclinical small animal studies. However, current optical imaging system for small animals has been heavily used in the past 10 years, and it has more frequently problematic for daily operation. In addition, the current one has limited capability for three-dimensional (3D) imaging, due to its lack of co-registration source. Therefore, we propose to purchase an upgraded optical imaging system with micro-CT component, and the proposed new system will be able to perform reliable co- registration for reproducible 3D imaging. The integrated optical imaging system, in conjunction with micro-CT functions, will provide much more precise imaging information than the optical imaging system alone. The proposed IVIS SpectrumCT is a unique instrumentation system that can enhance experimental protocols by incorporating best practices, to improve reliability and reproducibility in biomedical imaging and biomedical science. We propose to purchase a state-of-the-art an optical imaging system with micro-CT functions, which is capable of molecular imaging in transmission fluorescence, reflectance fluorescence, and bioluminescence modes in vivo, ex vivo, and in vitro. Significant advantages of the optical techniques possible with this system include the potential for multichannel imaging by using multiple probes with different spectral characteristics; quick, easy, and relatively low-cost rapid testing of biological hypotheses and proofs of principle in living experimental models. Importantly, optical bioluminescence imaging has unique advantages for detection of very low levels of signal because of its virtually background-free light emission. The micro-CT system will provide high-resolution images at a low X-ray dose to support 3D reconstruction and visualization. The combination of highly sensitive tomographic optical imaging systems IVIS Spectrum with micro-CT provides greater understanding of molecular events, and of anatomical reference and secondary effects of the disease process The new imaging system will be an important resource for many currently funded biomedical imaging research projects. Major projects include studies on neurodegenerative disorders and brain function, cancer, fibrosis of lung and liver, cardiovascular diseases, pancreatic islets in diabetes and transplantation. With the new imaging system and our existing imaging facilities under one roof, we can feasibly perform in-vivo experiments using one or more imaging modalities in succession, or even in parallel. This system will be an invaluable resource for the rich body of interdisciplinary research at the Martinos center and the larger MGH research community, as well as at other institutions in the greater Boston area.